2023 Fiscal Year Final Research Report
Establishment of carcinogenesis model of intestinal type gastric cancer from the organoid of atrophic gastritis patient.
| Project/Area Number |
21K07915
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | intestinal metaplasia / BMP / LGR5 / WNT / LATS2 / RUNX3 |
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| Outline of Final Research Achievements |
The organoid from atrophic gastritis patients contained LGR5-positive cells. WNT signaling is essential for the survival of LGR5-positive cells in vitro, and WNT3a positive cells located in the base of the gastric gland were thought to be the niche for LGR5 positive cells in atrophic gastritis patients.
LATS2 or RUNX3 knock out in organoid cells led to the CDX2 expression. LATS2 knock out was also induced ID4 upregulation. With these, BMP signaling activation is associated with intestinal metaplasia.LATS2 or RUNX3 knock out organoid cells acquired tumorigenic potential after TP53 or SMAD4 knock out in vivo.
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| Free Research Field |
gastric carcinogenesis
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| Academic Significance and Societal Importance of the Research Achievements |
胃発がんメカニズムの解析はこれまで進んでいないが、萎縮性胃炎患者検体から樹立したオルガノイドを用いることで、腸型胃がんの発がんメカニズムの解析が行えることが確認できた。
萎縮性胃炎から腸上皮化生に至るメカニズムにおいてはLATS2/RUNX3の遺伝子発現低下が関与しており、BMPシグナルが活性化が重要で、その後のがん化につながることが確認できた。
本結果から、腸上皮化生患者からの胃癌発症予防のためにBMPシグナルを抑制することが重要であると推察され、今後の胃癌発症予防に重要な研究結果と考える。
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